The purpose of this observational study is to characterize which immune system cells hide the latent reservoir of HIV by counting the number of latent HIV in different subsets of CD4 cells. Observations will also be made on other possible mechanisms of HIV persistence by looking at cellular factors such as APOBEC3 and drug transporters. The purpose of this study is to develop new strategies to reduce and possibly eliminate the latent reservoir in HIV infected adults.

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Establishment of a longitudinal, observational cohort of chemotherapeutically suppressed HIV participants to study cellular and virologic characteristics that enable HIV latency [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Characterization of memory CD4 cell subsets isolated from chemotherapeutically suppressed participants [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Quantification of the amount of latent HIV in each memory cell type in chemotherapeutically suppressed participants [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Evidence of HIV evolution [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Characterization of certain proteins in memory CD4-cell subsets in chemotherapeutically suppressed participants [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Determination of the association of protein regulation with cellular toxicity and the latent HIV reservoir in chemotherapeutically suppressed participants [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Characterization of the effects of immune activation on the latent reservoir of HIV [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Determination of the role of drug transporters in chemotherapeutically suppressed patients [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]

Intensively studied participants initiating potentially suppressive drug therapy. Group 1 participants may undergo optional leukapheresis. Group 1 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 1 participants will default to either Group 3 or Group 4.

2

Intensively studied, well-suppressed participants on HAART. Participants in Group 2 may undergo optional leukapheresis. Group 2 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 2 participants will default to either Group 3 or Group 4.

Intensively studied participants who are currently participating in the Merck Expanded Access Program and receiving raltegravir. Participants in Group 5 may undergo optional leukapheresis. Group 5 participants may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing from the study. If specimens are not obtained for any reason at any visit, Group 5 participants will default to either Group 3 or Group 4.

Detailed Description:

Memory CD4 cells may provide a reservoir of latent HIV that cannot be completely eliminated using currently available anti-HIV medications. The overall goal of this observational study is to develop new strategies to eliminate the latent HIV reservoir in HIV infected individuals. CD4-cell subsets, cellular anti-HIV factors, and cellular drug transporters will be observed to determine which resting memory cells hide latent HIV and to determine the mechanisms responsible for the persistence of the latent HIV reservoir.

This study will last for at least 3 years. The screening visit will include medical history, contact information, urine collection, and a physical exam. Participants will be assigned to one of five groups:

Group 1 will consist of intensively studied adults initiating potentially suppressive drug therapy. At the screening visit, Group 1 participants will be given the option to either undergo blood draws or leukapheresis for all visits.

Group 2 will consist of intensively studied, well-suppressed adults on highly active antiretroviral therapy (HAART). At the screening visit, Group 2 participants will be given the option to either undergo blood draws or leukapheresis for all visits.

Group 3 will consist of nonintensively studied adults initiating potentially suppressive drug therapy. Group 3 participants will undergo blood draws at all visits.

Group 4 will consist of nonintensively studied, well-suppressed adults on HAART. Group 4 participants will undergo blood draws at all visits.

Group 5 will consist of participants who are currently in the Merck Expanded Access Program receiving raltegravir. At the screening visit, Group 5 participants will be given the option to either undergo blood draws or leukapheresis for all visits.

For all participants undergoing blood draws only, visits will occur every 3 months for about 3 years. For patients undergoing leukapheresis, visits will occur every 6 months for about 3 years. At each visit, blood collection, documentation of current HAART, and updating of contact information will occur. Participants are encouraged to provide additional blood samples to be stored at all visits.

Participants in Groups 1, 2, or 5 may decline to be in the leukapheresis group at any time and will be given the option of continuing in the blood draw group or withdrawing completely from the study. If specimens are not obtained for any reason at any visit, participants in Groups 1, 2, or 5 will default to either Group 3 or Group 4. Antiretroviral medications will not be provided by this study.

Eligibility

Ages Eligible for Study:

18 Years to 65 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

Participants will be recruited from the Comprehensive Care Clinic, a clinic that provides care exclusively to HIV patients from middle Tennessee and surrounding states. Participants are screened and identified with the inclusion and exclusion criteria from the computerized medical records system. If the medical charts are tagged, the study nurse will speak to the selected participant at the participant's following appointment.

Criteria

Inclusion Criteria for Groups 1 and 3:

HIV infected

Antiretroviral therapy (ART) naive OR a history of treatment with highly active antiretroviral therapy (HAART), a currently detectable viral load greater than 500 copies/ml, about to begin second or later potentially suppressive antiretroviral regimen, and must meet the following two requirements:

Viral load less than 50 copies/ml on the immediately prior regimen with less than 50 copies/ml measured on at least two visits during prior ART

Viral load greater than 500 copies/ml on two consecutive visits and a history of failure during prior lamivudine- or emtricitabine-containing ART

Exclusion Criteria for Groups 1 and 3:

History of treatment with any two of the following: darunavir, tipranavir, or enfuvirtide

Self-reported or clinician-reported nonadherence to earlier ART

Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence

Weight less than 110 lbs

Blood transfusion within the 6 months prior to study entry

Platelets less than 50 cells/mm3

International normalized ratio (INR) greater than 2.0 if participants are on warfarin

Heart disease with recent angina or myocardial infarction (MI) within 1 year prior to study entry

Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less

Prior ART that included only one or two drugs

Pregnancy

Inclusion Criteria for Groups 2 and 4:

HIV infected

Currently on HAART with an undetectable viral load of less than 50 copies/ml for 12 months prior to study entry (at least two measures). If the participant is on the second or later regimen of HAART, the previous regimen must have contained lamivudine or emtricitabine.

Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence

Weight less than 110 lbs

Blood transfusion within the 6 months prior to study entry

Platelets less than 50 cells/mm3

INR greater than 2.0 if participants are on warfarin

Heart disease with recent angina or MI within 1 year prior to study entry

Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less

Prior ART that included only one or two drugs

Pregnancy

Inclusion Criteria for Group 5:

HIV infected

Currently taking or about to begin raltegravir with optimized background HAART

Exclusion Criteria:

Current substance abuse that, in the opinion of the investigator, will increase the risk of nonadherence

Weight less than 110 lbs

Blood transfusion 6 months prior to study entry

Platelets less than 50/mm3

INR greater than 2.0 if participants are on warfarin

Heart disease with recent angina or MI within 1 year prior to study entry

• Hematocrit 28% or less OR hemoglobin 8.0 g/dl or less

Pregnancy

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00581802